Whereas sleep is generally thought to be a relatively quiescent state, there is growing experimental and clinical evidence that significant perturbations in coronary hemodynamic and cardiac electrophysiologic function occur during rapid eye movement (REM) sleep and transitions from slow wave sleep. We found in canines that intensely phasic REM produces major surges in heart rate which are accompanied by a reduction in coronary flow in the stenosed coronary circulation. During transitions from slow wave sleep, there are abrupt pauses in heart rhythm which last up to 8 seconds. These observations may provide insights into the poorly understood clinical phenomena of nocturnal angina and cardiac standstill associated with sleep apnea. We plan to elucidate the neural mechanisms involved in these sleep-induced changes in heart rhythm and to quantify their impact during acute myocardial ischemia. We will employ our newly developed signal processing techniques which permit simultaneous tracking of rapid changes in autonomic nervous system activity and cardiac vulnerability by complex demodulation of heart rate variability and T-wave alternans (Science 252:437, 1991). Our specific aims are: l. To characterize the dynamic changes in autonomic nervous system activity and cardiac vulnerability during sleep by complex demodulation of heart rate variability and T-wave alternans in normal animals prior to and following pharmacologic and surgical denervation. 2. To define the influence of sleep state on the autonomic response and vulnerability to ventricular fibrillation during acute myocardial ischemia and reperfusion in neurally intact and denervated animals. The methods include sleep state determination based on EEG, EMG, EOG, hippocampal and lateral geniculate electrical activity, spectral analysis of electrocortical activity, and coronary hemodynamic and cardiac electrophysiologic function. The ultimate goal will be to shed light on the mechanisms involved in the genesis of life-threatening arrhythmias in individuals with coronary disease.